Sex differences in acute and chronic coronary syndromes

Ischemic heart disease (IHD), including acute coronary syndrome (ACS) and chronic coronary syndrome (CCS), remains the leading cause of morbidity and mortality worldwide, but affects women and men differently. Women are underrepresented in cardiovascular trials, and sex differences in clinical presentation, biology, and treatment may contribute to divergent outcomes. This thesis enhances understanding of sex differences in IHD in three parts.
Part I investigates sex differences in ACS in the Netherlands and describes the development of a national ACS registry. Using data from a large Dutch ACS registry, this thesis shows that women present at older age, have distinct risk profiles, and exhibit less extensive coronary artery disease than men. Despite this seemingly lower anatomical disease burden, younger women with ST-segment elevation myocardial infarction experience disproportionately unfavorable outcomes, underscoring a vulnerable subgroup requiring greater attention.
Part II explores biological and treatment-related sex differences in IHD, including plaque characteristics, biomarker trajectories, PCI outcomes, and bleeding risk. Women demonstrated more favorable coronary plaque characteristics and distinct biomarker patterns after ACS, suggesting sex-related differences in atherosclerosis and post-infarction recovery. PCI studies demonstrated similar long-term protection against stent thrombosis in women and men, while women had higher bleeding risk during dual antiplatelet therapy, largely driven by potentially preventable access-site complications.
Part III evaluates female-specific reproductive risk factors in acute chest pain assessment. These factors did not improve short-term risk prediction beyond established emergency department tools.
Overall, this thesis supports high-quality registries, stronger inclusion of women in research, and sex-stratified analyses to advance precision cardiovascular care.